Changes in lung volume and resistance to airflow which occur in chronic obstructive pulmonary disease decrease the length, increase the load, and diminish the efficiency of the diaphragm -- the major respiratory muscle. We hypothesize that as a consequence compensatory alterations in diaphragmatic muscle fiber composition; sarcomere number; intrinsic contractile properties; pattern of neural activation; synaptic function; and muscle blood flow occur facilitating diaphragmatic performance. Studies will be performed in a well-accepted animal model of emphysema produced by instillation of elastase into the airway. The severity of emphysema will be assessed from measurements of lung mechanics (e.g. FRC and airway resistance) and lung pathology. Histochemical techniques will be used to characterize muscle fiber composition. Sarcomere number and size will be determined by laser diffraction methods. Diaphragm function will be examined both from study of the tension generated by isolated muscle strips and from transdiaphragmatic pressure (Pdi) in spontaneously breathing animals. Muscle strip studies allow greater control of variables influencing muscle force and will be used to determine the effects of emphysema on different muscle force and will be used to determine the effects of emphysema on different regions of the diaphragm. The strength (length-tension relationship), endurance (tension-time relationship), and intrinsic contractile properties (contraction and relaxation times, twitch-tetanus ratio) of the costal, sternal and crural regions will be examined. Synaptic function will be assessed from the effects of d-tubocurare, a competitive inhibitor of acetylcholine, on the susceptibility to fatique and from microelectrode recordings of muscle end plate potentials. The magnitude of Pdi during resting and chemically stimulated breathing and during phrenic nerve stimulation will be used to characterize the function of the diaphragm in toto. Blood flow will be measured by the radioactive microsphere method. The pattern of neural activation will be assessed from the phrenic neurogram and diaphragm EMG recorded from the costal, sternal, and crural regions. Factors which influence diaphragmatic function and which may be therapeutically useful (e.g. nutrition, exercise, drugs) will be studied.